Complex catalyst, process for producing the complex catalyst, and process for producing alcohol derivative with the complex catalyst

ABSTRACT

There are provided (asymmetric) complex catalysts comprising metal complexes and Lewis acids as components, the metal complex being of formula (1):                  
 
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are the same or different and are independently hydrogen, halogen, alkyl or the like; one of R 9  and R 10  is hydrogen and the other is alkyl of 1 to 4 carbon atoms or the like; Q is a single bond or alkylene of 1 to 4 carbon atoms; M is a metal ion; and A is a balancing counter ion or ligand; processes for the production of these complex catalysts; processes for the production of (optically active) alcohol derivatives, characterized in that cyclic ether compounds are reacted with phenol derivatives in the presence of these complex catalysts; and further processes for producing (optically active) nitrogen-containing heterocyclic compounds by reacting these alcohol derivatives with halogenated nitrogen-containing heterocyclic compounds in the presence of a base.

TECHNICAL FIELD OF INVENTION

The present invention relates to a process for the production of alcoholderivatives and more particularly to a process for the regio- orstereo-selective production of alcohol derivatives as well as tocatalysts having excellent regio- and stereo-selectivity.

BACKGROUND ART

It has been known that 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,which is a nitrogen-containing heterocyclic compound having juvenilehormone activity, is produced by a process in which an alcoholderivative such as 1-methyl-2-(4-phenoxyphenoxy)ethanol is reacted witha halogenated nitrogen-containing heterocyclic compound such as2-chloropyridine in the presence of a base (JP 3034951 A). The alcoholderivative, 1-methyl-2-(4-phenoxyphenoxy)ethanol, which is anintermediate for production, has been produced by, for example, reactingpropylene oxide with 4-phenoxyphenol in the presence of a base. In thisprocess, however, in addition to the desired1-methyl-2-(4-phenoxyphenoxy)ethanol, there is also produced its isomer,2-methyl-2-(4-phenoxyphenoxy)ethanol, as a by-product; therefore, it isnecessary to separate and remove this isomer by a separating techniquesuch as crystallization. For this reason, the above process cannotalways be said to be a quite satisfactory process from an industrialpoint of view.

Further, for producing optically active nitrogen-containing heterocycliccompounds, it requires the step of treating an organic carboxylic acidester of the above alcohol derivative with a microorganism-derivedesterase to cause asymmetric hydrolysis, affording an optically activealcohol derivative. This cannot always be said to be quite satisfactoryfrom an industrial point of view in that the number of steps forproduction becomes increased.

PURPOSE OF THE INVENTION

The primary purpose of the invention is to provide an industriallyadvantageous process for the production of alcohol derivatives asdescribed above.

SUMMARY OF THE INVENTION

According to the process of the present invention, an alcohol derivativecan be obtained in a regio- and stereo-selective manner by the use of acatalyst as described below for the reaction of a cyclic ether compound,a typical example of which is propylene oxide, with a phenol derivative.In addition, by reacting the alcohol derivative obtained by this processwith a halogenated nitrogen-containing heterocyclic compound, thedesired nitrogen-containing heterocyclic compound can be produced inhigh yield.

That is, the present invention provides:

1. a complex catalyst comprising a metal complex and a Lewis acid ascomponents, the metal complex being of formula (1):

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are the same or different andare independently hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy,haloalkyl, haloalkoxy, hydroxyl, nitro, amino, carbamoyl, carboxyl,substituted or unsubstituted aryl, or silyl; or two adjacent groups ofR¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are combined together to represent anaphthalene ring by forming a ring together with a benzene ring to whichthey are attached;

one of R⁹ and R¹⁰ is hydrogen and the other is phenyl or naphthyloptionally substituted with at least one selected from the groupconsisting of alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbonatoms, haloalkyl, haloalkoxy and halogen; or either one pair of R⁹ andR¹⁰ attached to the different carbon atoms are combined together attheir ends to form a tetramethylene linkage and the other pair arehydrogen atoms;

Q is a single bond or alkylene of 1 to 4 carbon atoms; or Q is combinedwith R⁹ and R¹⁰ to represent 1,1′-binaphthyl attached to the nitrogenatoms at 2 and 2′ positions;

M is a metal ion; and

A is a balancing counter ion or ligand;

2. a process for the production of the above complex catalyst;

3. a process for the production of an alcohol derivative, characterizedin that a cyclic ether compound is reacted with a phenol derivative inthe presence of the above complex catalyst; and

4. the above production process comprising the step of reacting thealcohol derivative with a halogenated nitrogen-containing heterocycliccompound in the presence of a base to give a nitrogen-containingheterocyclic compound.

DETAILED DESCRIPTION OF THE INVENTION

First, the following will describe the metal complex catalyst of formula(1).

In the above formula (1), the halogen atom and the alkyl, alkenyl,alkynyl, alkoxy, haloalkyl, haloalkoxy, hydroxyl, nitro, amino,carbamoyl, carboxyl, aryl and silyl groups, which are represented by R¹,R², R³, R⁴, R⁵, R⁷ and R⁸, are defined below.

The halogen atom may include fluorine, chlorine, bromine and the like.

The alkyl group may include straight chain, branched chain or cyclicalkyl groups of 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,tert-pentyl, n-hexyl, cylcopentyl and cyclohexyl.

The alkoxy group may include straight chain, branched chain or cyclicalkoxy groups of 1 to 6 carbon atoms, such as methoxy, ethoxy,n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy,n-hexyloxy and cyclohexyloxy.

The haloalkyl group may include those obtained by substituting the abovehalogen atom(s) for one or more than one hydrogen atom of the abovealkyl, such as chloromethyl, chloroethyl, fluoromethyl andtrifluoromethyl.

The haloalkoxy group may include those obtained by substituting theabove halogen atom(s) for one or more than one hydrogen atom of theabove alkoxy, such as chloromethoxy, chloroethoxy, fluoroethoxy andtrifluoromethoxy.

The alkenyl group may include straight chain, branched chain or cyclicalkenyl groups of 2 to 6 carbon atoms, such as vinyl, propenyl,1-butenyl, 2-butenyl, 2-methyl-1-propenyl, pentenyl, hexenyl andcyclohexenyl.

The alkynyl group may include straight chain or branched chain alkynylgroups of 2 to 6 carbon atoms, such as ethynyl, propynyl, 1-butynyl,2-butynyl and hexynyl.

The substituted or unsubstituted aryl group may include aryl groupsoptionally substituted with methyl, nitro or methoxy, such as phenyl,toluyl, xylyl, nitrophenyl, methoxyphenyl and naphthyl.

The silyl group may include silyl groups tri-substituted withhydrocarbon groups, and the hydrocarbon groups may include C₁₋₄ alkyl oraryl. Specific examples thereof may include trimethylsilyl,triethylsilyl, triphenylsilyl and tert-butyldimethylsilyl.

Two adjacent groups of R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are combinedtogether to represent a naphthalene ring together with a benzene ring towhich they are attached.

In the above formula (1), one of R⁹ and R¹⁰ is hydrogen and the other isphenyl or naphthyl optionally substituted with at least one selectedfrom the group consisting of C₁₋₄ alkyl, C₁₋₄ alkoxy, haloalkyl wherethe alkyl group is halogenated, haloalkoxy where the alkoxy group ishalogenated, and halogen. Alternatively, either one pair of R⁹ and R¹⁰attached to the different carbon atoms are combined together to form atetramethylene linkage. In this case, the other pair are hydrogen atoms.

The C₁₋₄ alkyl group may include straight chain or branched chain alkylgroups such as methyl, ethyl, n-propyl, isopropyl, n-butyl andtert-butyl.

The C₁₋₄ alkoxy group may include straight chain or branched chainalkoxy groups such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxyand tert-butoxy.

The halogen atom may include fluorine, chlorine, bromine and the like.The phenyl or naphthyl group optionally substituted with at least oneselected from the group consisting of C₁₋₄ alkyl, C₁₋₄ alkoxy,haloalkyl, haloalkoxy and halogen may include phenyl, 1-naphthyl,2-naphthyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-chlorophenyl,3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl,4-fluorophenyl, 4-bromophenyl, 2-trifluoromethylphenyl,3-trifluoromethylphenyl and 4-trifluoromethylphenyl.

The alkylene group of 2 to 4 carbon atoms, which is represented by Q,may include methylene, ethylene, trimethylene and tetramethylene.

In the above formula (1), M is a metal ion and A is a balancing counterion or ligand. For example, when the ionic valence of a metal ion isequal to the coordination number of ligands, A is not present. When theionic valence of a metal ion is different from the coordination number,A is a counter ion or ligand.

The metal ion may include cobalt ion, chromium ion and manganese ion.The counter ion or ligand may include halogen ions such as chloride ion,perfluoroalkoxide ions such as nonafluoro-tert-butoxide ion, acetateligands, and phenolate ligands corresponding to phenol derivatives,which are used in the reaction of cyclic ether compounds with phenolderivatives as described below. In particular, preferred are acetateligands and phenolate ligands corresponding to phenol derivatives, whichare used in the reaction of cyclic ether compounds with phenolderivatives as described below.

In the present specification, the halogen atom and the alkyl, alkylene,alkenyl, alkynyl and aryl groups found in the compounds of formulas (2)to (6′) refer to the same as described above, unless otherwiseindicated.

The above metal complexes of formula (1) may include the following metalcomplexes of formula (1a), optically active metal complexes of formula(1′) and optically active metal complexes of formula (1′a).

More specifically, the metal complexes of formula (1a) corresponding tothe above formula (1) wherein Q is a single bond:

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, M and A are as definedabove.

Further, the optically active metal complexes of formula (1′):

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, M, A and Q are asdefined above.

The optically active metal complexes of the following formula (1′a)corresponding to the above formula (1′) wherein Q is a single bond:

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, M and A are as definedabove.

The metal complexes of formula (1) or (1a) may include:

-   N,N′-bis(salicylidene)-1,2-ethylenediamino cobalt (III) acetate,-   N,N′-bis(salicylidene)-1,2-ethylenediamino cobalt (III)    4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) hexafluoroisopropoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) hexafluoroisopropoxide,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III) acetate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III)    nonafluoro-tert-butoxide,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III)    4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) acetate,-   N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) hexafluoroisopropoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) acetate,-   N,N′-bis(3,5-di-tert-pentylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    cobalt (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    cobalt (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino chromium(III) acetate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino chromium (III)    nonafluoro-tert-butoxide,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino chromium (III)    4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    chromium (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    chromium (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino manganese (III)    acetate,-   N,N′-bis(salicylidene)-1,2-cyclohexanediamino manganese (III)    4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    manganese (III) nonafluoro-tert-butoxide,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis[5-methyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis[5-methyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) acetate,-   N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) acetate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) nonafluoro-tert-butoxide,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) 4-phenoxyphenolate,-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    manganese (III) acetate, and-   N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    manganese (III) 4-phenoxyphenolate.

The optically active metal complexes of formula (1′) or (1′a) mayinclude:

-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) hexafluoroisopropoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III)    acetate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III)    nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino cobalt (III)    4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis[(5-methyl-3-(1-methyl-1-phenylethyl)salicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) hexafluoroisopropoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    cobalt (III) 4-phenoxyphenolate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    cobalt (III) acetate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    cobalt (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino    chromium (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    chromium (III) 4-phenoxyphenolate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    chromium (III) acetate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    chromium (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(salicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methylsalicylidene)-1,2-cyclohexanediamino    manganese (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-nitrosalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-chlorosalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis[5-methyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis[5-methyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3-tert-butyl-5-triphenylmethylsalicylidene)-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis[5-tert-butyl-3-(1-methyl-1-phenylethyl)salicylidene]-1,2-cyclohexanediamino    manganese (III) 4-phenoxyphenolate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) acetate,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) nonafluoro-tert-butoxide,-   (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diphenylethylenediamino    manganese (III) 4-phenoxyphenolate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    manganese (III) acetate,-   (R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,1′-binaphthalene-2,2′-diamino    manganese (III) 4-phenoxyphenolate, and

similar optically active metal complexes in which the aboveconfiguration (R,R)-(−) or (R)-(+) is changed to (S,S)-(+) or (S)-(−),respectively.

The Lewis acid may include aluminum halides, dialkyl aluminum halides,trialkoxy aluminum, titanium halides, tetraalkoxy titanium, boronhalides and zinc halides.

The aluminum halides may include aluminum chloride and aluminum bromide.The dialkyl aluminum halides may include diethyl aluminum chloride,diethyl aluminum bromide and diisopropyl aluminum chloride. Thetrialkoxy aluminum may include triethoxy aluminum, triisopropoxyaluminum and tri-tert-butoxy aluminum. The titanium halides may includetitanium tetrachloride. The tetraalkoxy titanium may includetetraisopropoxy titanium. The boron halides may include borontrifluoride, boron trichloride and boron tribromide. The zinc halidesmay include zinc chloride and zinc bromide.

The Lewis acid may be used as such or as a solution in an organicsolvent. The Lewis acid, which is unstable to, for example, air or waterand which requires careful handling, may preferably be used as asolution in an organic solvent. The organic solvent is not particularlylimited, so long as it is inert to the Lewis acid, and may includealiphatic hydrocarbon solvents such as hexane and heptane; and ethersolvents such as diethyl ether and tert-butyl methyl ether. Further,complex compounds of Lewis acids such as boron trifluoride-diethyl ethercomplex compounds may also be used.

The amount of Lewis acid used is not particularly limited, but isusually 0.2 to 5 moles, preferably 0.5 to 2 moles, relative to 1 mole ofmetal complex (1).

The metal complex catalyst of the present invention can be produced byreacting metal complex (1) with a Lewis acid, and the reaction isusually carried out in an organic solvent by contacting and mixing bothof them. When both of them are contacted and mixed, the reaction willoccur to form a novel complex. The production of a novel (asymmetric)complex is achieved by, for example, mixing both of them in an organicsolvent, which causes the change of color in the reaction mixture,thereby making it possible to verify that the metal complex is beingreacted with the Lewis acid to form a novel (asymmetric) complex. Forexample, when(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate is mixed with aluminum chloride intert-butyl methyl ether, the color of the mixture changes from brown todark green.

The reaction temperature in the reaction of metal complex (1) with aLewis acid is usually −50 to 50° C., preferably −25 to 40° C.

The organic solvent may include ether solvents such as diethyl ether andtert-butyl methyl ether; aromatic hydrocarbon solvents such as toluene;halogenated hydrocarbon solvents such as chlorobenzene and chloroform;and aliphatic hydrocarbon solvents such as hexane. The amounts for theiruse are not particularly limited.

If, for example, water is present in the reaction system, Lewis acidsare easily decomposed; therefore, the reagents, solvents to be used andthe like may preferably be subjected to dehydration in advance ordehydrating agents such as molecular sieves may preferably be allowed tocoexist in the reaction system.

When metal complex (1) is reacted with a Lewis acid in an organicsolvent, the solution containing a novel complex catalyst produced maybe used as such in the reaction of cyclic ether compound (2) with phenolderivative (3), or the novel complex catalyst may be separated beforeuse by, for example, concentration of the above solution.

In this step, the use of a metal complex of formula (1′) or (1′a) makesit possible to obtain an asymmetric complex catalyst. The reaction ofcyclic ether compound (2) with phenol derivative (3) in the presence ofthis catalyst makes it possible to the desired optically active alcoholderivative by the reaction exhibiting excellent regio- andstereo-selectivity.

Next, the following will describe the step of reacting a cyclic ethercompound with a phenol derivative in the presence of the complexcatalyst obtained above to give an alcohol derivative.

The cyclic ether compound may be any reactive cyclic ether compoundwhich causes ring-opening reaction by the reaction with a phenolderivative, and may include cyclic ether compounds of the followingformula (2):

(hereinafter abbreviated as cyclic ether compound (2))wherein R¹³ is hydrogen; R¹⁴ is hydrogen or alkyl; or R¹³ and R¹⁴ arecombined together to represent alkylene of 2 to 6 carbon toms; R¹⁵ isalkyl, aryl or, aralkyl; wherein the alkyl, aryl or aralkyl group mayhave a substituent(s); and n is 0 or 1.

When the cyclic ether compound has an asymmetric carbon atom(s) in themolecule, it may be an optically active form or a mixture of theoptically active forms.

The alkyl group represented by R¹⁴ may include alkyl groups of 1 to 4carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl andisobutyl. The alkylene group of 2 to 6 carbon atoms formed by combiningR¹³ and R¹⁴ together may include ethylene, propylene, butylene,pentylene and hexylene.

Further, R¹⁵ represents alkyl, aryl or aralkyl. The alkyl group mayinclude the same as described for R¹⁴. The aryl group may include phenyland naphthyl. The aralkyl group may include those composed of such alkyland aryl groups, and may include benzyl and phenylethyl. These alkyl,aryl and aralkyl groups may have a substituent(s), and thesubstituent(s) which may include halogen as described above, such aschlorine and fluorine, hydroxyl and alkoxy such as methoxy and ethoxy.

Specific examples of cyclic ether compound (2) may include propyleneoxide, 1,2-epoxybutane, 1,2-epoxyhexane, 1,3-epoxyhexane,1,2-epoxy-4-methylpentane, 1,2-epoxy-3-phenylpropane, styrene oxide,1-chloro-2,3-epoxypropane, 1-bromo-2,3-epoxypropane,2,3-epoxy-1-propanol, cyclohexene oxide, cyclopentene oxide and1,2-epoxycyclooctane.

The preferred cyclic ether compound may include propylene oxide and1,2-epoxybutane.

The phenol derivative may be any phenol having a phenolic hydroxyl groupor any thiophenol derivative obtained by replacing the oxygen atom inthe hydroxyl group of the phenol derivative by a sulfur atom, which mayinclude phenol derivatives of formula (3):

(hereinafter abbreviated as phenol derivative (3))wherein X is oxygen or sulfur; R¹⁶'s are the same or different and areindependently hydrogen, halogen, nitro, alkyl of 1 to 6 carbon atoms,alkoxy of 1 to 6 carbon atoms, phenylthio, benzyl or phenoxy; and m isan integer of 0 to 5; wherein the alkyl group of 1 to 6 carbon atoms,the alkoxy group of 1 to 6 carbon atoms, the phenylthio, benzyl orphenoxy group may optionally be substituted with alkyl of 1 to 4 carbonatoms, alkoxy of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms,haloalkoxy of 1 to 4 carbon atoms or halogen.

The halogen atom, the alkyl group of 1 to 6 carbon atoms and the alkoxygroup of 1 to 6 carbon atoms, which are represented by R¹⁶, may includethe same as described above. The haloalkyl group of 1 to 4 carbon atomsmay include chloromethyl and trifluoromethyl. The haloalkoxy group of 1to 4 carbon atoms may include chloromethoxy.

The phenol derivative may include compounds of the above formula (3)wherein R¹⁶ is hydrogen, halogen, nitro, alkyl of 1 to 4 carbon atoms,alkoxy of 1 to 4 carbon atoms, or phenoxy; provided that the alkyl groupof 1 to 4 carbon atoms, the alkoxy group of 1 to 4 carbon atoms, or thephenoxy group may optionally be substituted with alkyl of 1 to 4 carbonatoms, alkoxy of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms,haloalkoxy of 1 to 4 carbon atoms, or halogen; and

phenol derivatives of formula (3a):

wherein X is oxygen or sulfur; Y is oxygen, sulfur or methylene; R_(a)'sare independently halogen or methyl; R_(b)'s are the same or differentand are independently hydrogen, halogen, alkyl of 1 to 4 carbon atoms,alkoxy of 1 to 4 carbon atoms, or trifluoromethyl; p is an integer of 0to 4; and q is an integer of 0 to 2.

The phenol derivative (3) may include phenol, 4-chlorophenol,2-bromophenol, 4-bromophenol, o-cresol, m-cresol, p-cresol,4-methoxyphenol, 4-phenoxyphenol, 4-nitrophenol,2,3-difluoro-6-nitrophenol, thiophenol, 2-bromo-4-methylthiophenol,4-chlorothiophenol, 4-methoxythiophenol, 4-phenoxythiophenol,4-(3-methylphenoxy)phenol, 4-(2-fluorophenoxy)phenol,4-(3-fluorophenoxy)phenol, 4-(4-fluorophenoxy)phenol,4-(3,5-difluorophenoxy)phenol, 4-(3,5-dichlorophenoxy)phenol,4-(3-trifluoromethylphenoxy)phenol, 4-(3-methoxyphenoxy)phenol,4-benzylphenol and 4-phenoxythiophenol.

The preferred phenol derivative (3) may include 4-phenoxyphenol,4-(3-methylphenoxy)phenol, 4-(2-fluorophenoxy)phenol,4-(3-fluorophenoxy)phenol, 4-(4-fluorophenoxy)phenol,4-(3,5-difluorophenoxy)phenol, 4-(3,5-di-chlorophenoxy)phenol,4-(3-trifluoromethylphenoxy)phenol, 4-(3-methoxyphenoxy)phenol,4-benzylphenol and 4-phenoxythiophenol.

The amount of cyclic ether compound used is usually 1 mole or more (2moles or more when an asymmetric complex catalyst is used), relative to1 mole of phenol derivative, and there is no particular upper limitthereof. Since too large amounts may easily result in an economicaldisadvantage, the amount thereof is practically 5 moles or less (10moles or less when an asymmetric complex catalyst is used).

The complex catalyst comprising metal complex (1) and a Lewis acid,although it exhibits sufficient activity in a catalytic amount, mayexhibit sufficient catalytic activity, preferably in amounts for useranging from 0.1 to 3 mol %, relative to 1 mole of phenol derivative. Ofcourse, amounts larger than 3 mol % may be used; however, larger amountsfor use will easily result in an economical disadvantage. Therefore,practical amounts for use are as described above.

The reaction temperature is usually −50 to 50° C., preferably −25 to 40°C.

The reaction is achieved by contacting or mixing a complex catalyst,which has been obtained by reacting metal complex (1) with a Lewis acid;a cyclic ether compound and a phenol derivative. The order of mixing isnot particularly limited.

The reaction is usually carried out in the presence of an organicsolvent. The organic solvent may include single or mixed solventsselected from aliphatic hydrocarbon solvents such as hexane and heptane;aromatic hydrocarbon solvents such as toluene; ether solvents such asdiethyl ether and tert-butyl methyl ether; and halogenated hydrocarbonsolvents such as chloroform and chlorobenzene. The amounts for their useare not particularly limited.

After completion of the reaction, the reaction mixture containing analcohol derivative may be used as such in the subsequent step or, forexample, the reaction mixture may be subjected to concentration toseparate the alcohol derivative, which is then used in the subsequentstep. Further, for example, water and, if necessary, a water-insolubleorganic solvent may be added to the reaction mixture, followed byextraction, providing the organic layer containing the alcoholderivative, which organic layer may be used in the subsequent step ormay be subjected to concentration to separate the alcohol derivative,which is then used in the subsequent step. The separated alcoholderivative may be further purified by an ordinary means of purification,such as distillation, recrystallization and column chromatography, andthen used in the subsequent step. The water-insoluble organic solventmay include aromatic hydrocarbon solvents such as toluene and xylene;aliphatic hydrocarbon solvents such as hexane and heptane; halogenatedhydrocarbon solvents such as chloroform and chlorobenzene; and ethersolvents such as diethyl ether and tert-butyl methyl ether. The amountsfor their use are not particularly limited.

The above cyclic ether compound (2) is reacted with the above phenolderivative (3) to give an alcohol derivative of formula (4):

(hereinafter abbreviated as alcohol derivative (4))wherein R¹³, R¹⁴, R¹⁵, R¹⁶, X, m and n are as defined above.

The above alcohol derivative may include alcohol derivatives of thefollowing formula (4a):

(hereinafter abbreviated as alcohol derivative (4a))wherein R¹³, R¹⁴, R¹⁵, R_(a), R_(b), X, Y, n, p and q are as definedabove.

The alcohol derivatives (4) and (4a) thus obtained may include:

-   1-phenoxy-2-propanol,-   1-(4-chlorophenoxy)-2-propanol,-   1-(2-bromophenoxy)-2-propanol,-   1-(4-bromophenoxy)-2-propanol,-   1-(2-methylphenoxy)-2-propanol,-   1-(3-methylphenoxy)-2-prop anol,-   1-(4-methylphenoxy)-2-propanol,-   1-(4-methoxyphenoxy)-2-propanol,-   1-(4-phenoxyphenoxy)-2-propanol,-   1-(4-nitrophenoxy)-2-propanol,-   1-(2,3-difluoro-6-nitrophenoxy)-2-propanol,-   1-phenylthio-2-propanol,-   1-(2-bromo-4-methylphenylthio)-2-propanol,-   1-(4-chlorophenylthio)-2-propanol,-   1-(4-methoxyphenylthio)-2-propanol,-   1-(4-phenoxyphenylthio)-2-propanol,-   1-phenoxy-2-butanol,-   1-(4-chlorophenoxy)-2-butanol,-   1-(2-bromophenoxy)-2-butanol,-   1-(4-bromophenoxy)-2-butanol,-   1-(2-methylphenoxy)-2-butanol,-   1-(3-methylphenoxy)-2-butanol,-   1-(4-methylphenoxy)-2-butanol,-   1-(4-methoxyphenoxy)-2-butanol,-   1-(4-phenoxyphenoxy)-2-butanol,-   1-(4-nitrophenoxy)-2-butanol,-   1-(2,3-difluoro-6-nitrophenoxy)-2-butanol,-   1-phenylthio-2-butanol,-   1-(2-bromo-4-methylphenylthio)-2-butanol,-   1-(4-chlorophenylthio)-2-butanol,-   1-(4-methoxyphenylthio)-2-butanol,-   1-(4-phenoxyphenylthio)-2-butanol,-   1-phenoxy-2-hexanol,-   1-(4-chlorophenoxy)-2-hexanol,-   1-(2-bromophenoxy)-2-hexanol,-   1-(4-bromophenoxy)-2-hexanol,-   1-(2-methylphenoxy)-2-hexanol,-   1-(3-methylphenoxy)-2-hexanol,-   1-(4-methylphenoxy)-2-hexanol,-   1-(4-methoxyphenoxy)-2-hexanol,-   1-(4-phenoxyphenoxy)-2-hexanol,-   1-(4-nitrophenoxy)-2-hexanol,-   1-(2,3-difluoro-6-nitrophenoxy)-2-hexanol,-   1-phenylthio-2-hexanol,-   1-(2-bromo-4-methylphenylthio)-2-hexanol,-   1-(4-chlorophenylthio)-2-hexanol,-   1-(4-methoxyphenylthio)-2-hexanol,-   1-(4-phenoxyphenylthio)-2-hexanol,-   2-phenoxy-1-phenylethanol,-   2-(4-chlorophenoxy)-1-phenylethanol,-   2-(2-bromophenoxy)-1-phenylethanol,-   2-(4-bromophenoxy)-1-phenylethanol,-   2-(2-methylphenoxy)-1-phenylethanol,-   2-(3-methylphenoxy)-1-phenylethanol,-   2-(4-methylphenoxy)-1-phenylethanol,-   2-(4-methoxyphenoxy)-1-phenylethanol,-   2-(4-phenoxyphenoxy)-1-phenylethanol,-   2-(4-nitrophenoxy)-1-phenylethanol,-   2-(2,3-difluoro-6-nitrophenoxy)-1-phenylethanol,-   2-phenylthio-1-phenylethanol,-   2-(2-bromo-4-methylphenylthio)-1-phenylethanol,-   2-(4-chlorophenylthio)-1-phenylethanol,-   2-(4-methoxyphenylthio)-1-phenylethanol,-   2-(4-phenoxyphenylthio)-1-phenylethanol,-   3-phenoxy-1-chloro-2-propanol,-   3-(4-chlorophenoxy)-1-chloro-2-propanol,-   3-(2-bromophenoxy)-1-chloro-2-propanol,-   3-(4-bromophenoxy)-1-chloro-2-propanol,-   3-(2-methylphenoxy)-1-chloro-2-propanol,-   3-(3-methylphenoxy)-1-chloro-2-propanol,-   3-(4-methylphenoxy)-1-chloro-2-propanol,-   3-(4-methoxyphenoxy)-1-chloro-2-propanol,-   3-(4-phenoxyphenoxy)-1-chloro-2-propanol,-   3-(4-nitrophenoxy)-1-chloro-2-propanol,-   3-(2,3-difluoro-6-nitrophenoxy)-1-chloro-2-propanol,-   3-phenylthio-1-chloro-2-propanol,-   3-(2-bromo-4-methylphenylthio)-1-chloro-2-propanol,-   3-(4-chlorophenylthio)-1-chloro-2-propanol,-   3-(4-methoxyphenylthio)-1-chloro-2-propanol,-   3-(4-phenoxyphenylthio)-1-chloro-2-propanol,-   3-phenoxy-1-bromo-2-propanol,-   3-(4-chlorophenoxy)-1-bromo-2-propanol,-   3-(2-bromophenoxy)-1-bromo-2-propanol,-   3-(4-bromophenoxy)-1-bromo-2-propanol,-   3-(2-methylphenoxy)-1-bromo-2-propanol,-   3-(3-methylphenoxy)-1-bromo-2-propanol,-   3-(4-methylphenoxy)-1-bromo-2-propanol,-   3-(4-methoxyphenoxy)-1-bromo-2-propanol,-   3-(4-phenoxyphenoxy)-1-bromo-2-propanol,-   3-(4-nitrophenoxy)-1-bromo-2-propanol,-   3-(2,3-difluoro-6-nitrophenoxy)-1-bromo-2-propanol,-   3-phenylthio-1-bromo-2-propanol,-   3-(2-bromo-4-methylphenylthio)-1-bromo-2-propanol,-   3-(4-chlorophenylthio)-1-bromo-2-propanol,-   3-(4-methoxyphenylthio)-1-bromo-2-propanol,-   3-(4-phenoxyphenylthio)-1-bromo-2-propanol,-   3-phenoxy-1,2-propanediol,-   3-(4-chlorophenoxy)-1,2-propanediol,-   3-(2-bromophenoxy)-1,2-propanediol,-   3-(4-bromophenoxy)-1,2-propanediol,-   3-(2-methylphenoxy)-1,2-propanediol,-   3-(3-methylphenoxy)-1,2-propanediol,-   3-(4-methylphenoxy)-1,2-propanediol,-   3-(4-methoxyphenoxy)-1,2-propanediol,-   3-(4-phenoxyphenoxy)-1,2-propanediol,-   3-(4-nitrophenoxy)-1,2-propanediol,-   3-(2,3-difluoro-6-nitrophenoxy)-1,2-propanediol,-   3-phenylthio-1,2-propanediol,-   3-(2-bromo-4-methylphenylthio)-1,2-propanediol,-   3-(4-chlorophenylthio)-1,2-propanediol,-   3-(4-methoxyphenylthio)-1,2-propanediol,-   3-(4-pheoxyphenylthio)-1,2-propanediol,-   2-phenoxycyclohexanol,-   2-(4-chlorophenoxy)cyclohexanol,-   2-(2-bromophenoxy)cyclohexanol,-   2-(4-bromophenoxy)cyclohexanol,-   2-(2-methylphenoxy)cyclohexanol,-   2-(3-methylphenoxy)cyclohexanol,-   2-(4-methylphenoxy)cyclohexanol,-   2-(4-methoxyphenoxy)cyclohexanol,-   2-(4-phenoxyphenoxy)cyclohexanol,-   2-(4-nitrophenoxy)cyclohexanol,-   2-(2,3-difluoro-6-nitrophenoxy)cyclohexanol,-   2-(phenylthio)cyclohexanol,-   2-(2-bromo-4-methylphenylthio)cyclohexanol,-   2-(4-chlorophenylthio)cyclohexanol,-   2-(4-methoxyphenylthio)cyclohexanol,-   2-(4-phenoxyphenylthio)cyclohexanol,-   2-phenoxycyclopentanol,-   2-(4-chlorophenoxy)cyclopentanol,-   2-(2-bromophenoxy)cyclopentanol,-   2-(4-bromophenoxy)cyclopentanol,-   2-(2-methylphenoxy)cyclopentanol,-   2-(3-methylphenoxy)cyclopentanol,-   2-(4-methylphenoxy)cyclopentanol,-   2-(4-methoxyphenoxy)cyclopentanol,-   2-(4-phenoxyphenoxy)cyclopentanol,-   2-(4-nitrophenoxy)cyclopentanol,-   2-(2,3-difluoro-6-nitrophenoxy)cyclopentanol,-   2-(phenylthio)cyclopentanol,-   2-(2-bromo-4-methylphenylthio)cyclopentanol,-   2-(4-chlorophenylthio)cyclopentanol,-   2-(4-methoxyphenylthio)cyclopentanol,-   2-(4-phenoxyphenylthio)cyclopentanol,-   2-phenoxycyclooctanol,-   2-(4-chlorophenoxy)cyclooctanol,-   2-(2-bromophenoxy)cyclooctanol,-   2-(4-bromophenoxy)cyclooctanol,-   2-(2-methylphenoxy)cyclooctanol,-   2-(3-methylphenoxy)cyclooctanol,-   2-(4-methylphenoxy)cyclooctanol,-   2-(4-methoxyphenoxy)cyclooctanol,-   2-(4-phenoxyphenoxy)cyclooctanol,-   2-(4-nitrophenoxy)cyclooctanol,-   2-(2,3-difluoro-6-nitrophenoxy)cyclooctanol,-   2-(phenylthio)cyclooctanol,-   2-(2-bromo-4-methylphenylthio)cyclooctanol,-   2-(4-chlorophenylthio)cyclooctanol,-   2-(4-methoxyphenylthio)cyclooctanol, and-   2-(4-phenoxyphenylthio)cyclooctanol.

The amount of a regio-isomer of the following formula (7):

produced as a by-product, which regio-isomer is a by-product in thisstep, is very small.

The process of reacting the above cyclic ether compound (2) with theabove phenol derivative (3) in the presence of an asymmetric complexcatalyst makes it possible to obtain an optically active alcoholderivative of formula (4′):

(hereinafter abbreviated as optically active alcohol derivative (4′))wherein R¹³, R¹⁴, R¹⁵, R¹⁶, X, m and n are as defined above and *indicates an asymmetric carbon atom.

The above alcohol derivative may include alcohol derivatives of thefollowing formula (4′a):

(hereinafter abbreviated as alcohol derivative (4′a)) wherein R¹³, R¹⁴,R¹⁵, R_(a), R_(b), X, Y, n, p and q are as defined above and * indicatesan asymmetric carbon atom.

The optically active alcohol derivatives (4′) and (4′a) thus obtainedmay include:

-   optically active 1-(4-phenoxyphenoxy)-2-propanol,-   optically active 1-[4-(3-methylphenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(2-fluorophenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(3-fluorophenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(4-fluorophenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(3,5-difluorophenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(3,5-dichlorophenoxy)phenoxy]-2-propanol,-   optically active 1-[4-(3-trifluoromethylphenoxy)]-2-propanol,-   optically active 1-[4-(3-methoxyphenoxy)phenoxy]-2-propanol,-   optically active 1-(4-benzylphenoxy)-2-propanol,-   optically active 1-(4-phenylthiophenoxy)-2-propanol,-   optically active 1-(4-phenoxyphenoxy)-2-butanol,-   optically active 1-[4-(3-methylphenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(2-fluorophenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(3-fluorophenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(4-fluorophenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(3,5-difluorophenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(3,5-dichlorophenoxy)phenoxy]-2-butanol,-   optically active 1-[4-(3-trifluoromethylphenoxy)]-2-butanol,-   optically active 1-[4-(3-methoxyphenoxy)phenoxy]-2-butanol,-   optically active 1-(4-benzylphenoxy)-2-butanol, and optically active    1-(4-phenylthiophenoxy)-2-butanol.

Next, the following will describe the step of reacting the alcoholderivative obtained above with a halogenated nitrogen-containingheterocyclic compound in the presence of a base to give anitrogen-containing heterocyclic compound. In this step, an opticallyactive alcohol derivative can be reacted with a halogenatednitrogen-containing heterocyclic compound in the presence of a base togive an optically active nitrogen-containing heterocyclic compound.

The halogenated nitrogen-containing heterocyclic compound may be anynitrogen-containing heterocyclic compound having a halogen atom whichcan be reacted with the hydroxyl group of the above alcohol derivative,and may include halogenated nitrogen-containing heterocyclic compoundsof the formula (5):Z-R¹⁷  (5)(hereinafter abbreviated as halogenated nitrogen-containing heterocycliccompound (5))wherein Z is halogen and R¹⁷ is pyridyl, pyridazinyl, pyrimidinyl,pyrazinyl, triazinyl, 2-thiazolyl or dihydro-2-thiazolyl; wherein thesegroups may optionally have one or more than one substituent selectedfrom the group consisting of halogen, alkyl of 1 to 4 carbon atoms,alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms,trifluoromethyl or nitro.

The halogen atom, the alkyl group of 1 to 4 carbon atoms and the alkoxygroup of 1 to 4 carbon atoms may include the same as described above.The alkylthio group of 1 to 4 carbon atoms may include methylthio,ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio,sec-butylthio and tert-butylthio.

The pyridyl group may include 2-pyridyl, 3-pyridyl and 4-pyridyl. Thepyridazinyl group may include 3-pyridazinyl. The pyrimidinyl group mayinclude 2-pyrimidinyl and 4-pyrimidinyl. The pyrazinyl group may include2-pyrazinyl. The triazinyl group may include 1,3,5-triazin-2-yl.

The halogenated nitrogen-containing heterocyclic compound (5) mayinclude:

-   2-fluoropyridine, 2-chloropyridine, 2-bromopyridine,-   3-chloropyridine, 4-chloropyridine, 2-chloro-5-methylpyridine,-   2-chloro-6-methylpyridine, 2-chloro-5-nitropyridine,-   2,5-dichloropyridine, 2-chloro-3-nitropyridine,-   2,3-dichloro-5-trifluoromethylpyridine,-   2-chloro-3,4,5,6-tetrafluoropyridine,-   2-chloro-6-fluoropyridine, 2-chloropyrazine,-   3,6-dichloropyridazine, 2-chloro-1,3-thiazole,-   2-chloro-5-nitro-1,3-thiazole,-   2-chloro-4,5-dihydro-1,3-thiazole,-   2-chloro-4,4-dimethyl-5-hydro-1,3-thiazole,-   2-chloro-4,5-dihydro-4-methyl-1,3-thiazole,-   2-chloro-4,5-dihydro-1,3-thiazine, 2-chloropyrimidine,-   2-chloro-4,6-dimethylpyrimidine,-   4-chloro-2,6-dimethylpyrimidine,-   2,4,6-trichloro-1,3,5-triazine, and-   2-chloro-4,6-dimethylthio-1,3,5-triazine.

The amount of halogenated nitrogen-containing heterocyclic compound usedis usually 0.5 to 10 moles, preferably 0.8 to 2 moles, relative to 1mole of alcohol derivative.

The base may include alkali metals such as sodium and potassium; alkyllithium such as n-butyl lithium; alkali metal halides such as sodiumhydride; alkali metal amides such as lithium amide; alkali metalhydroxides such as sodium hydroxide and potassium hydroxide; alkalimetal carbonates such as sodium carbonate and potassium carbonate; andorganic bases such as triethylamine. The amounts for their use areusually 1 to 2 moles, relative to 1 mole of halogenatednitrogen-containing heterocyclic compound.

The reaction is usually carried out in the presence of an organicsolvent. The organic solvent may include single or mixed solventsselected from aprotic polar solvents such as N,N-dimethylformamide anddimethylsulfoxide; ether solvents such as tetrahydrofuran anddimethoxyethane; and aromatic hydrocarbon solvents such as toluene; ormixed solvents of these organic solvents and water. The amount ofsolvent used is not particularly limited. When mixed solvents of organicsolvents and water are used, phase transfer catalysts such asbenzyltriethyl ammonium chloride and tetra(n-butyl) ammonium bromide maybe used so that the reaction can proceed more smoothly.

The reaction temperature is usually in the range of −80° C. to thereflux temperature of the reaction mixture, preferably in the range of10° C. to the reflux temperature of the reaction mixture.

After completion of the reaction, for example, water and, if necessary,a water-insoluble organic solvent are added to the reaction mixture,followed by extraction, and the resulting organic layer is subjected toconcentration to separate the desired (optically active)nitrogen-containing heterocyclic compound. The separated (opticallyactive) nitrogen-containing heterocyclic compound may be furtherpurified by an ordinary means of purification such as recrystallization,column chromatography and distillation.

The above alcohol derivative (4) is reacted with the above halogenatednitrogen-containing heterocyclic compound (5) to give anitrogen-containing heterocyclic compound of formula (6):

wherein X, R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, X and n are as defined above.

In the above reaction, the use of alcohol derivatives of the aboveformula (4a) and (4′a) makes it possible to obtain nitrogen-containingheterocyclic compounds in which hydrogen atoms of hydroxyl groups informula (4a) and (4′a) have been replaced by R¹⁷.

The nitrogen-containing heterocyclic compound (6) thus obtained mayinclude:

-   2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-methyl-2-(3-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-methyl-2-[4-(3-methylphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-(2-methyl-4-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-methyl-2-[4-(2-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(4-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(3,5-dichlorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(3-trifluoromethylphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-[4-(3-methoxyphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-(4-benzylphenoxy)ethoxy]pyridine,-   2-[1-methyl-2-(4-phenoxythiophenoxy)ethoxy]pyridine,-   6-methyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   6-methyl-3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-fluoro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   6-methoxy-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-chloro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-chloro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-chloro-5-trifluoromethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-fluoro-2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyridine,-   5-fluoro-2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrazine,-   6-chloro-3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridazine,-   2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]thiazoline,-   2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]thiazoline,-   2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]thiazoline,-   5-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]thiazoline,-   2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyrimidine,-   2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyrimidine,-   6-chloro-4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   6-methylthio-4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   4,6-dimethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   2,6-dimethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-3,5-dimethylthio-1,3,5-triazine,-   2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-ethyl-2-(3-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3-methylphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-(2-methyl-4-phenoxyphenoxy)ethoxy]pyridine,-   2-[1-ethyl-2-[4-(2-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(4-fluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3,5-dichlorophenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3-trifluoromethylphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-[4-(3-methoxyphenoxy)phenoxy]ethoxy]pyridine,-   2-[1-ethyl-2-(4-benzylphenoxy)ethoxy]pyridine,-   2-[1-ethyl-2-(4-phenoxythiophenoxy)ethoxy]pyridine,-   6-methyl-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   6-methyl-3-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-nitro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-fluoro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   6-methoxy-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   5-chloro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-chloro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-nitro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   4-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   3-chloro-5-trifluoromethyl-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   5-fluoro-2-[1-ethyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyridine,    and-   5-fluoro-2-[1-ethyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine.

The above optically active alcohol derivative (4′) is reacted with theabove halogenated nitrogen-containing heterocyclic compound (5) to givean optically active nitrogen-containing heterocyclic compound of formula(6′):

(hereinafter abbreviated as optically active nitrogen-containingheterocyclic compound (6′))wherein R¹¹, R¹², R¹³, R¹⁴, R¹⁵, X, Y, n and * are as defined above.

The optically active nitrogen-containing heterocyclic compound (6′) thusobtained may include:

-   optically active 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active 2-[1-methyl-2-(3-phenoxyphenoxy)ethoxy]pyridine,-   optically active    2-[1-methyl-2-[4-(3-methylphenoxy)phenoxy]ethoxy]-pyridine,-   optically active    2-[1-methyl-2-(4-phenoxy-2-methylphenoxy)ethoxy]-pyridine,-   optically active    2-[1-methyl-2-[4-(2-fluorophenoxy)phenoxy]ethoxy]-pyridine,-   optically active    2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]-pyridine,-   optically active    2-[1-methyl-2-[4-(4-fluorophenoxy)phenoxy]ethoxy]-pyridine,-   optically active    2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-methyl-2-[4-(3,5-dichlorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-methyl-2-[4-(3-trifluoromethylphenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-methyl-2-[4-(3-methoxyphenoxy)phenoxy]ethoxy]pyridine,-   optically active 2-[1-methyl-2-(4-benzylphenoxy)ethoxy]pyridine,-   optically active    2-[1-methyl-2-(4-phenoxythiophenoxy)ethoxy]pyridine,-   optically active    6-methyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    6-methyl-3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    5-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    5-fluoro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    6-methoxy-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    5-chloro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    3-chloro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    3-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active 3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active 4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    3-chloro-5-trifluoromethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    5-fluoro-2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]-ethoxy]pyridine,-   optically active    5-fluoro-2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrazine,-   optically active    6-chloro-3-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyridazine,-   optically active 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]thiazoline,-   optically active    2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]-thiazoline,-   optically active    2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]thiazoline,-   optically active    5-nitro-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-thiazoline,-   optically active 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   optically active    2-[1-methyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]-pyrimidine,-   optically active    2-[1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyrimidine,-   optically active    6-chloro-4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-pyrimidine,-   optically active    6-methylthio-4-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   optically active    4,6-dimethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   optically active    2,6-dimethyl-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyrimidine,-   optically active    2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]-3,5-di-methylthio-1,3,5-triazine,-   optically active 2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active 2-[1-ethyl-2-(3-phenoxyphenoxy)ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3-methylphenoxy)phenoxy]ethoxy]-pyridine,-   optically active    2-[1-ethyl-2-(4-phenoxy-2-methylphenoxy)ethoxy]-pyridine,-   optically active    2-[1-ethyl-2-[4-(2-fluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3-fluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(4-fluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3,5-dichlorophenoxy)phenoxy]ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3-trifluoromethylphenoxy)phenoxy]-ethoxy]pyridine,-   optically active    2-[1-ethyl-2-[4-(3-methoxyphenoxy)phenoxy]ethoxy]-pyridine,-   optically active 2-[1-ethyl-2-(4-benzylphenoxy)ethoxy]pyridine,-   optically active 2-[1-ethyl-2-(4-phenoxythiophenoxy)ethoxy]pyridine,-   optically active    6-methyl-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    6-methyl-3-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    5-nitro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    5-fluoro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    6-methoxy-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]-pyridine,-   optically active    5-chloro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    3-chloro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    3-nitro-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active 3-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active 4-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    3-chloro-5-trifluoromethyl-2-[1-ethyl-2-(4-phenoxyphenoxy)ethoxy]pyridine,-   optically active    5-fluoro-2-[1-ethyl-2-[4-(3-fluorophenoxy)phenoxy]-ethoxy]pyridine,    and-   optically active    5-fluoro-2-[1-ethyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy]pyridine.

EXAMPLES

The present invention will be further illustrated by reference to thefollowing examples; however, the present invention is not limited tothese examples. The yields were calculated from the results of analysisby high performance liquid chromatography. The optical purity ofoptically active alcohol derivatives and the optical purity of opticallyactive nitrogen-containing heterocyclic compounds were calculated fromthe results of analysis by high performance liquid chromatography usingoptically active columns (CHIRALCEL OD: available from DAICEL CHEMICALINDUSTRIES, LTD.) and optically active columns (CHIRALCEL OJ-H:available from DAICEL CHEMICAL INDUSTRIES, LTD.), respectively.

Example 1

A nitrogen-purged 200-mL separable flask was charged with 404 mg of(R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate and 10 mL of tert-butyl methyl ether, towhich 147 mg of tetraisopropoxy titanium was added, and the mixture wasstirred at room temperature for 1 hour to prepare a catalyst solution(the color of the catalyst solution changed from brown to slightlygreenish brown). To the catalyst solution were added 9.41 g of4-phenoxyphenol and 10 mL of tert-butyl methyl ether, and the mixturewas cooled to the internal temperature of 5° C., after which 13.2 g ofpropylene oxide was added dropwise over 30 minutes. The mixture was keptstirred at the same temperature for 8 hours to achieve the reaction,followed by addition of water and extraction with ethyl acetate. Fromthe resulting organic layer, the solvent was distilled out to give asolid substance containing (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol.

The yield of (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol: 98% (based on4-phenoxyphenol); optical purity: 98% e.e.

To a suspension prepared by suspending 1.14 g of sodium hydride (60 wt %oil suspension) in 40 mL of N,N-dimethylformamide was slowly added underice cooling a solution prepared by dissolving the solid substance (purecontent: 5.34 g) obtained above in 20 g of N,N-dimethylformamide,followed by keeping stirred at room temperature for 1 hour. Then 3.64 gof 2-chloropyridine was added, and the mixture was stirred at theinternal temperature of 60° C. for 10 hours to achieve the reaction.Then ice water was poured into the reaction mixture, which was extractedthree times with ethyl acetate. The resulting organic layer wasconcentrated to give a solid substance containing(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

The yield of (S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine:91% (based on (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol); and opticalpurity: 98% e.e.

Example 2

A nitrogen-purged 50-mL Schlenk's tube was charged with 81 mg of(R,R)-(−)-N,N-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate and 1 mL of tert-butyl methyl ether, towhich 13 mg of anhydrous aluminum chloride and 1 g of molecular sieves3A were added, and the mixture was stirred at room temperature for 1hour to prepare a catalyst solution. With the lapse of time, the colorof the catalyst solution changed from brown to dark green. To the darkgreen catalyst solution were added 960 mg of 4-phenoxyphenol and 1.47 gof propylene oxide, and the mixture was stirred at room temperature for20 hours to achieve the reaction. After completion of the reaction,tert-butyl methyl ether was distilled out to give an oily substancecontaining (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol.

The yield of (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol: 82% (based on4-phenoxyphenol); and optical purity: 92% e.e.

The resulting oily substance containing(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 3

In Example 2, 0.1 mL of a diethyl aluminum chloride/hexane solution wasused in place of anhydrous aluminum chloride, and the color of thecatalyst solution changed from brown to dark green by the addition of adiethyl aluminum chloride/hexane solution. Then 4-phenoxyphenol andpropylene oxide were added to the dark green catalyst solution toachieve the reaction in the same manner as described in Example 2. Thus(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 72% yield andthe optical purity was 87% e.e.

The resulting (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 4

In Example 2, 26 mg of tri-tert-butoxy aluminum was used in place ofanhydrous aluminum chloride, and the color of the catalyst solutionchanged from brown to slightly greenish brown by the addition oftri-tert-butoxy aluminum. Then 4-phenoxyphenol and propylene oxide wereadded to the slightly greenish brown catalyst solution to achieve thereaction in the same manner as described in Example 2. Thus(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 68% yield andthe optical purity was 87% e.e.

The resulting (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 5

In Example 2, 16 mg of tri-tert-ethoxy aluminum was used in place ofanhydrous aluminum chloride, and the color of the catalyst solutionchanged from brown to slightly greenish brown by the addition oftri-tert-ethoxy aluminum. Then 4-phenoxyphenol and propylene oxide wereadded to the slightly greenish brown catalyst solution to achieve thereaction in the same manner as described in Example 2. Thus(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 83% yield andthe optical purity was 90% e.e.

The resulting (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 6

In Example 2, 29 mg of tetraisopropoxy titanium was used in place ofanhydrous aluminum chloride, and the color of the catalyst solutionchanged from brown to slightly greenish brown by the addition oftetraisopropoxy titanium. Then 4-phenoxyphenol and propylene oxide wereadded to the slightly greenish brown catalyst solution to achieve thereaction in the same manner as described in Example 2. Thus(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 84% yield andthe optical purity was 95% e.e.

The resulting (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 7

In Example 2, the amount of(R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate used was changed to 41 mg, and 15 mg oftetraisopropoxy titanium was used in place of anhydrous aluminumchloride, and the color of the catalyst solution changed from brown toslightly greenish brown by the addition of tetraisopropoxy titanium.Then 4-phenoxyphenol and propylene oxide were added to the slightlygreenish brown catalyst solution to achieve the reaction in the samemanner as described in Example 2. Thus(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 77% yield andthe optical purity was 94% e.e.

The resulting (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was reacted with2-chloropyridine in the same manner as described in Example 1 to give(S)-(+)-2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 8

A nitrogen-purged 50-mL Schlenk's tube was charged with 404 mg of(R,R)-(−)-N,N-bis(3,5-di-tert-butylsalicylidene)-1,2-cylcohexanediaminocobalt (III) 4-phenoxyphanolate and 10 mL of tert-butyl ethyl ether, andthe IR spectrum of the reaction mixture was measured. Then 147 mg oftetraisopropoxy titanium was added, and the color of the reactionmixture was changed from brown to slightly greenish brown. The peaks at752 cm⁻¹ and 956 cm⁻¹ appeared in addition to the peaks from(R,R)-(−)-N,N-bis(3,5-ditert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate, tert-butyl methyl ether andtetraisopropoxy titanium.

Comparative Example 1

A nitrogen-purged 50-mL Schlenk's tube was charged with 202 mg of(R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) 4-phenoxyphenolate, 1 g of molecular sieves 3A, 960 mg of4-phenoxyphenol and 1.47 g of propylene oxide, and the mixture wasstirred at room temperature for 20 hours to achieve the reaction. Aftercompletion of the reaction, the solvent was distilled out to give anoily substance containing (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol. Theoily substance was analyzed by high performance liquid chromatography inthe same manner as described in Example 1 to reveal that the yield of(S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was 14% (based on4-phenoxyphenol) and the optical purity was 77% e.e.

Comparative Example 2

A nitrogen-purged 50-mL Schlenk's tube was charged with 960 mg of4-phenoxyphenol and 1 mL of tert-butyl ethyl ether, to which 13 mg ofanhydrous aluminum chloride, 1 g of molecular sieves 3A and 1.47 g ofpropylene oxide were added, and the mixture was stirred at roomtemperature for 20 hours to achieve the reaction. After completion ofthe reaction, tert-butyl methyl ether was distilled out to give an oilysubstance. The oily substance was analyzed by high performance liquidchromatography to reveal that the main component was 4-phenoxyphenol andthe recovery of 4-phenoxyphenol was 93%.

Example 9

A nitrogen-purged 200-mL separable flask was charged with 170 mg ofN,N′-bis(salicylidene)-1,2-diphenylethylenediamino cobalt (III)4-phenoxyphenolate and 10 mL of tert-butyl methyl ether, to which 733 mgof tetraisopropoxy titanium was added, and the mixture was stirred atroom temperature for 1 hour to prepare a catalyst solution (the color ofthe catalyst solution changed from brown to slightly greenish brown). Tothe catalyst solution were added 9.41 g of 4-phenoxyphenol and 10 mL oftert-butyl methyl ether, and the mixture was cooled to the internaltemperature of 5° C. To this was added dropwise 6.6 g of propylene oxideover 30 minutes, and the mixture was then stirred at 5° C. for 8 hoursto achieve the reaction. After completion of the reaction, tert-butylmethyl ether was distilled out to give an oily substance containing1-(4-phenoxyphenoxy)-2-propanol. The oily substance was quantitated byhigh performance liquid chromatography (hereinafter abbreviated as LC)to reveal that the yield of 1-(4-phenoxyphenoxy)-2-propanol was 93%(based on 4-phenoxyphenol) and isomer ratio 1 was 0.001.

Isomer ratio 1 was calculated by the following equation:Isomer ratio 1=[LC area value of 2-(4-phenoxyphenoxy)-1-propanol]/[LCarea value of 2-(4-phenoxyphenoxy)-1-propanol+LC area value of1-(4-phenoxyphenoxy)-2-propanol]

To the resulting oily substance (pure content: 10.5 g) were added 6.5 gof 2-chloropyridine and 3.5 g of sodium hydroxide (granular), followedby mixing with stirring at the internal temperature of 100° C. Thenazeotropic dehydration was carried out at the internal temperature of150° C., operation pressure of 70 Torr (corresponding to 9.3 kPa) toachieve the reaction for 3 hours. Then the remaining 2-chloropyridinewas distilled out at the internal temperature of 157° C., operationpressure of 10 Torr (corresponding to 1.3 kPa), followed by cooling. Tothe reaction mixture were added water and toluene, and the mixture wasfiltered through Celite. The filtrate was extracted with toluene, andthe resulting organic layer was concentrated to give2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine. Yield: 90%. Isomerratio 2 was 0.001.

Isomer ratio 2 was calculated by the following equation:Isomer ratio 2={LC area value of2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine}/{LC area value of2-[1-methyl-2-(4-phenoxyphenoxy)-ethoxy]pyridine+LC area value of2-[2-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine}

Example 10

A nitrogen-purged 50-mL Schlenk's tube was charged with 26 mg ofN,N′-bis(salicylidene)-ethylenediamine cobalt (III) 4-phenoxyphenolateand 1 mL of tert-butyl methyl ether, to which 74 mg of tetraisopropoxytitanium was added, and the mixture was stirred at room temperature for1 hour to prepare a catalyst solution. To the catalyst solution wereadded 960 mg of 4-phenoxyphenol and 1.47 g of propylene oxide, and themixture was then stirred at room temperature for 20 hours to achieve thereaction. After completion of the reaction, tert-butyl methyl ether wasdistilled out to give an oily substance containing1-(4-phenoxyphenoxy)-2-propanol. Yield: 92% (based on 4-phenoxyphenol).Isomer ratio 1=0.003 (isomer ratio 1 was calculated by the same equationas described above in Example 9).

The resulting oily substance containing 1-(4-phenoxyphenoxy)-2-propanolis reacted with 2-chloropyridine in the same manner as described inExample 9 to give 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

Example 11

In Example 9, the reaction was carried out in the same manner asdescribed in Example 9, except that 17 mg ofN,N′-bis(salicylidene)-1,2-diphenylethylenediamino cobalt (III)4-phenoxyphenolate was used in place of 26 mg ofN,N′-bis(salicylidene)-ethylenediamino cobalt (III) 4-phenoxyphenolateand the amount of tert-butyl methyl ether used for the preparation of acatalyst was changed to 2 mL, 1-(4-phenoxyphenoxy)-2-propanol wasobtained in 95% yield and isomer ratio 1=0.003 (isomer ratio 1 wascalculated by the same equation as described above in Example 9).

The resulting oily substance containing 1-(4-phenoxyphenoxy)-2-propanolis reacted with 2-chloropyridine in the same manner as described inExample 9 to give 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine.

INDUSTRIAL APPLICABILITY

According to the present invention, novel (asymmetric) complex catalystsobtained by reaction of (optically active) metal complexes with Lewisacids exhibit high catalytic activity in the reaction of cyclic ethercompounds with phenol derivatives; therefore, it is possible to produce(optically active) alcohol derivatives in an industrially advantageousmanner by reacting cyclic ether compounds with phenol derivatives in thepresence of these (asymmetric) complex catalysts, and it is possible toobtain (optically active) nitrogen-containing heterocyclic compounds inan industrially advantageous manner by reacting these resulting(optically active) alcohol derivatives with halogenatednitrogen-containing heterocyclic compounds in the presence of a base.

1. A complex catalyst comprising, as components, a Lewis acid and ametal complex of formula (1):

 wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are the same or different andare independently hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy,haloalkyl, haloalkoxy, hydroxyl, nitro, amino, carbamoyl, carboxyl,substituted or unsubstituted aryl, or silyl; or two adjacent groups ofR¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are combined together to represent anaphthalene ring by forming a ring together with a benzene ring to whichthey are attached; one of R⁹ and R¹⁰ is hydrogen and the other is phenylor naphthyl optionally substituted with at least one selected from thegroup consisting of alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4carbon atoms, haloalkyl, haloalkoxy and halogen; or either one pair ofR⁹ and R¹⁰ attached to the different carbon atoms are combined togetherat their ends to form a tetramethylene linkage and the other pair arehydrogen atoms; Q is a single bond or alkylene of 1 to 4 carbon atoms;or Q is combined with R⁹ and R¹⁰ to represent 1,1′-binaphthyl attachedto the nitrogen atoms at 2 and 2′ positions; M is cobalt ion, a chromiumion or a manganese ion; and A is a balancing counter ion or ligand,wherein the Lewis acid is selected from the group consisting of analuminum halide, a dialkyl aluminum halide, a trialkoxy aluminum, atitanium halide, a tetraalkoxy titanium, a boron halide and a zinchalide.
 2. A complex catalyst according to claim 1, wherein the metalcomplex is an optically active metal complex of formula (1′):

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, M, A and Q are asdefined in formula (1).
 3. A complex catalyst according to claim 1,wherein Q is a single bond.
 4. A complex catalyst according to claim 2,wherein Q is a single bond.
 5. A process for the production of a metalcomplex catalyst according to claim 1, characterized in that a metalcomplex of formula (1) is reacted with a Lewis acid selected from thegroup consisting of an aluminum halide, a dialkyl aluminum halide, atrialkoxy aluminum, a titanium halide, a tetraalkoxy titanium, a boronhalide and a zinc halide.
 6. A process for the production of an alcoholderivative of the following formula (4):

wherein R¹³, R¹⁴, R¹⁵, R¹⁶, X, m and n are as defined below,characterized in that a cyclic ether compound of formula (2):

wherein R¹³ is hydrogen; R¹⁴ is hydrogen or alkyl; or R¹³ and R¹⁴ arecombined together to represent alkylene of 2 to 6 carbon atoms; R⁵ isalkyl, aryl or aralkyl; where the alkyl, aryl and aralkyl groups mayoptionally have a substituent(s); and n is 0 or 1, is reacted with aphenol derivative of the following formula (3):

wherein X is oxygen or sulfur; R¹⁶'s are the same or different and areindependently hydrogen, halogen, nitro, alkyl of 1 to 6 carbon atoms,alkoxy of 1 to 6 carbon atoms, phenylthio, benzyl or phenoxy; where thealkyl group of 1 to 6 carbon atoms, the alkoxy group of 1 to 6 carbonatoms, the phenylthio, benzyl or phenoxy group may optionally besubstituted with alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbonatoms, haloalkyl of 1 to 4 carbon atoms, haloalkoxy of 1 to 4 carbonatoms, or halogen; and m is an integer of 0 to 5, in the presence of acomplex catalyst according to claim
 1. 7. A production process accordingto claim 8, comprising the further step of reacting the alcoholderivative of formula (4) with a halogenated nitrogen-containingheterocyclic compound of formula (5):Z—R¹⁷  (5) wherein Z is halogen and R¹⁷ is pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, 2-thiazolyl or dihydro-2-thiazolyl;wherein these groups may optionally have one or more than onesubstituent selected from the group consisting of halogen, alkyl of 1 to4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4carbon atoms, trifluoromethyl and nitro, to give a nitrogen-containingheterocyclic compound of formula (6):

wherein X, R¹³, R¹⁴, R¹⁵, R¹⁶, m and n are as defined in claim
 6. 8. Aprocess for the production of an optically active alcohol derivative ofthe following formula (4):

wherein R¹³, R¹⁴, R¹⁵, R¹⁶, X, m and n are as defined below and *indicates an asymmetric carbon atom, characterized in that a cyclicether compound of formula (2):

wherein R¹³ is hydrogen; R¹⁴ is hydrogen or alkyl; or R¹³ and R¹⁴ arecombined together to represent alkylene of 2 to 6 carbon atoms; R¹⁵ isalkyl, aryl or aralkyl; where the alkyl, aryl or aralkyl group mayoptionally have a substituent(s); and n is 0 or 1, is reacted with aphenol derivative of the following formula (3):

wherein X is oxygen or sulfur; R¹⁶'s are the same or different and areindependently hydrogen, halogen, nitro, alkyl of 1 to 6 carbon atoms,alkoxy of 1 to 6 carbon atoms, phenylthio, benzyl or phenoxy; whereinthe alkyl group of 1 to 6 carbon atoms, the alkoxy group of 1 to 6carbon atoms, the phenylthio, benzyl or phenoxy group may optionally besubstituted with alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbonatoms, haloalkyl of 1 to 4 carbon atoms, haloalkoxy of 1 to 4 carbonatoms, or halogen; and m is an integer of 0 to 5, in the presence of anasymmetric complex catalyst according to claim
 2. 9. A productionprocess according to claim 8, comprising the further step of reactingthe optically active alcohol derivative of formula (4′) with ahalogenated nitrogen-containing heterocyclic compound of formula (5):Z—R¹⁷  (5) wherein Z is halogen and R¹⁷ is pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, triazinyl, 2-thiazolyl or dihydro-2-thiazolyl;wherein these groups may optionally have one to two substituentsselected from the group consisting of halogen, alkyl of 1 to 4 carbonatoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms,trifluoromethyl and nitro in the presence of a base to give an opticallyactive nitrogen-containing heterocyclic compound of formula (6′):

wherein R¹³, R¹⁴, R¹⁵, X, m, n and * are as defined in claim
 8. 10. Aproduction process according to claim 7 or 9, wherein R¹³ is hydrogen;R¹⁴ is hydrogen; R¹⁵ is methyl or ethyl; R¹⁶ is hydrogen, halogen, alkylof 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, ortrifluoromethyl; and n is an integer of 0 to 1.